The use of microfluidic technology has been proposed for a number of analytical chemical and biochemical operations. This technology allows one to perform chemical and biochemical reactions, macromolecular separations, and the like, that range from the simple to the relatively complex, in easily automated, high-throughput, low-volume systems. The term “microfluidic” refers to a system or device having micron or submicron scale channels and chambers. In general, microfluidic systems include a microfluidic device, or chip, that has networks of integrated submicron channels in which materials are transported, mixed, separated and detected. Microfluidic systems typically also contain components that provide fluid driving forces to the chip and that detect signals emanating from the chip.
Microfluidic chips may be fabricated from a number of different materials, including glass or polymeric materials. An example of a commercially available microfluidic chip is shown in FIG. 1. FIG. 1A is a topside view of the chip, and FIG. 1B is a bottom side view of the same chip. That chip, a DNA LacChip® manufactured by Caliper Life Sciences, Inc. of Mountain View Calif., is used with the Agilent 2100 Bioanalyzer system manufactured by Agilent Technologies, Inc. of Palo Alto Calif. The chip in FIG. 1 has two major components: a working part 128 made of glass, and a plastic caddy or mount 127 bonded to the working part. The working part contains microfluidic channels in its interior, and wells on its exterior that provide access to the microfluidic channels. The working part is typically fabricated by bonding together two or more planar substrate layers. The microfluidic channels in the working part are formed when one planar substrate encloses grooves formed on another planar substrate. The mount protects the working part of the chip, and provides for easier handling of the chip by a user. The increased ease of handling partially results from the fact that the mount 127 is larger than the working part of the device, which in many cases is too small and thin to be easily handled. The mount may be fabricated from any suitable polymeric material, such as an acrylic or thermoplastic. The glass working part is typically bonded to the polymeric mount using a UV-cured adhesive. Reservoirs 129 in the mount 127 provide access to the wells on the working part of the chip. The reservoirs 129 hold much greater volumes of material than the wells in the working part 128, thus providing an interface between the macro-environment of the user and the microenvironment of the wells and channels of the microfluidic device. Although the use of the plastic mount 127 to hold the working part 128 provides several advantages, the use of the mount may have some disadvantages. For example, the polymeric material of the mount 127 may cause dye interaction and surface chemistry issues with respect to the materials applied to the reservoirs. Further, mount 127 and the adhesive used to adhere mount 127 to the working part may affect the life span of the chip when shipped and stored.
The type of microfluidic chip in FIG. 1 is a “planar” chip. In a planar chip, the only access to the microchannels in the chip is through the reservoirs 129 in the caddy and in-turn through the wells in the working part 128. Another type of microfluidic chip is a “sipper” chip, which has a small tube or capillary (the “sipper”) extending from the chip through which fluids stored outside the chip can be directed into the microfluidic channels in the chip. Typical sipper chips have between one and twelve sippers. In use, the sipper is placed in a receptacle having sample material and minute quantities of the sample material are introduced, or “sipped” through the capillary tube to the microfluidic channels of the chip. This sipping process can be repeated to introduce any number of different sample materials into the chip. Sippers make it easier to carry out high-throughput analysis of numerous samples on a single microfluidic chip.
Microfluidic chips fabricated from glass are typically shipped after having been preconditioned or “primed” with sodium hydroxide under pressure. The preconditioning process prepares the surface of the chip for use and increases the lifetime of the chip. The extremely caustic nature of the preconditioning fluid makes it desirable to have the preconditioning performed by technicians prior to shipping as opposed to having the end user apply the sodium hydroxide. The chips are then shipped in liquid to preserve the preconditioned surface state. In many cases, it may also be desirable to precondition or prime microfluidic chips fabricated from polymeric materials, and to ship those chips in a liquid to preserve a preconditioned surface state. Regardless of the chip material, and the surface treatment requirements associated with that material, microfluidic chips often need to be primed, i.e. filled with liquid, before they can be used to perform analyses.
Current shipping and storage methods for primed microfluidic chips typically entail the use of a fluid-filled container. The fluid is generally distilled water containing a preservative such as EDTA or a buffer such as tris-tricine. When a chip is placed in a container, it is submerged in the fluid and suspended in the submerged position. This type of shipping container is undesirable for various reasons. First, the end user must “fish” the chip out of the fluid in which it has been shipped. Secondly, the submersion may weaken the adhesive bonding between the laminated substrate layers in the chip, or the bonding between the working part of the chip and a mounting fixture holding the working part of the chip. Those types of delamination may render the chip unusable. Finally, as the chips are capable of being reused many times, the user must replace the chips into the storage fluid between uses, which increases the risk of contaminating the chip.
Although microfluidic devices have become advanced enough that multiple analyses can be performed on a single chip using very small volumes of sample material, the preparation and handling of chips often requires a great deal of human effort and time. The reservoirs on a chip are also vulnerable to evaporation and/or current leakage between reservoirs causing changes in concentration of sample materials or in fluid flow through the chip, which can make the chip function inaccurately.
Several macro-scale automatic reader and liquid handling devices have been developed for transferring material into and out of, and monitoring the output (e.g. level of fluorescence) of reactions carried out in standard 96, 192, 384 and 1536 well microtiter plates. Such devices are particularly useful for liquid handling or detection. However, the microtiter plates used in conjunction with such macro-scale devices provide limited functionality as compared with microfluidic devices, since microtiter plates do not allow for the type fluid movement that can take place within microfluidic devices. Although the macro-scale devices designed for used with microtiter plates do have some liquid handling capability, this capability is not particularly suited for the types of operations that can be performed on microfluidic chips. Furthermore, liquid handling devices and automatic readers are not conventionally integrated into a single machine.